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The structure of a highly virulent Theiler's murine encephalomyelitis virus (GDVII) and implications for determinants
1Center for Macromolecular Crystallography, University of Alabama at Birmingham 35294, USA.
Abstract:
GDVII is a highly virulent Theiler's murine encephalomyelitis virus (TMEV) which causes acute encephalitis in mice, while the BeAn and DA strains are the less virulent TMEV which cause chronic demyelinating disease in the central nervous system as a result of persistent infection. Purified GDVII virus isolated from infected BHK-21 cells was crystallized and its structure was determined to 3.5-A resolution by X-ray crystallography. In contrast to other TMEV structures, the VP1 C-terminus of GDVII virus has an ordered conformation that forms a hook over the VP3 knob near the threefold axis. Comparisons with the atomic structures of the less virulent BeAn and DA viruses revealed significant structural variations in a major site (cluster B) on the protruding surface loop puff B of VP2. Puff B is located near the VP3 GH loop region which is structurally analogous to the host receptor attachment site of the major serogroup of human rhinoviruses. Mutations at residue 1101 in VP1 and residue 2141 in VP2, which are also near the VP3 GH loop and adjacent to cluster B, were previously shown to influence persistence of DA virus. These observations indicate that the characteristic interaction with the host receptor through these sites may potentially alter TMEV persistence.
Insights
Structural differences in Theiler's murine encephalomyelitis virus (TMEV) strains influence viral persistence. Theiler's murine encephalomyelitis virus (TMEV) structure variations may alter host receptor interactions, impacting disease outcomes.
Area of Science:
- Virology
- Structural Biology
- Neuroscience
Background:
- Theiler's murine encephalomyelitis virus (TMEV) causes varying neurological diseases in mice.
- Highly virulent GDVII strain causes acute encephalitis, while less virulent BeAn and DA strains cause chronic demyelinating disease.
Purpose of the Study:
- To determine the crystal structure of the virulent GDVII strain of TMEV.
- To compare the structure of GDVII with less virulent TMEV strains (BeAn and DA).
- To identify structural variations potentially linked to TMEV persistence and host receptor interaction.
Main Methods:
- X-ray crystallography was used to determine the 3.5-A resolution structure of purified GDVII virus.
- Comparative structural analysis was performed between GDVII and BeAn/DA TMEV strains.
Main Results:
- The GDVII virus structure revealed an ordered VP1 C-terminus forming a hook, unlike other TMEV structures.
- Significant structural variations were identified in VP2's protruding surface loop (puff B) between GDVII and less virulent strains.
- Puff B is located near the VP3 GH loop, analogous to human rhinovirus receptor attachment sites.
Conclusions:
- Structural variations, particularly in VP2 puff B and near the VP3 GH loop, may influence TMEV's ability to persist.
- These sites are adjacent to known mutation sites affecting viral persistence, suggesting a role in host receptor interaction and disease outcome.